Current (and future) applications of MALDI mass spectrometry in the identification and characterization of clinically-relevant microorganisms for research, clinical and regulatory laboratories

Authors: Fagerquist, Clifton - Keith

Submitted to: Meeting Proceedings
Publication Type: Proceedings
Publication Acceptance Date: 11/1/2018
Publication Date: 6/21/2019
Citation: Fagerquist, C.K. 2019. Current (and future) applications of MALDI mass spectrometry in the identification and characterization of clinically-relevant microorganisms for research, clinical and regulatory laboratories. Meeting Proceedings. ASM Microbe 2019, June 20-24, 2019, San Francisco, CA.

Interpretive Summary:

Technical Abstract: Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) is increasingly utilized in research, clinical and regulatory labs for routine analysis of clinically important microorganisms. The Food and Drug Administration (FDA) within the past several years approved two commercial MALDI instruments that utilize a time-of-flight (TOF) mass analyzer for use in taxonomic identification of bacteria. This approval facilitated the use of MALDI-TOF-MS in clinical laboratories in hospitals in the USA. Prior to the FDA action, MALDI-TOF-MS had been approved for use in clinical labs in Europe. In addition to the MS hardware, commercial software was developed to easily analyze MALDI-TOF-MS data using pattern recognition algorithms and/or principal component analysis. The software rapidly compares the MS spectrum or “fingerprint” of a bacterial unknown to spectra of hundreds or thousands of known bacterial strains available in commercial libraries or in libraries constructed in-house with known strains. The highest scoring match above a pre-set confidence level indicates an identification. Microorganism identification by MS relies upon detection of peptides and small proteins (< 20 kDa) that are abundant enough to ionize efficiently by MALDI from an unfractionated bacterial cell lysate or intact whole cell analysis. These peptide and protein ion peaks collectively constitute the MS “fingerprint”, however, the identity of these ions are not known necessarily nor is their identity crucial to microorganism identification using pattern recognition algorithms. However, there is an urgent need to extend beyond simple taxonomic identification to characterization. For example, assessing pathogenicity and antimicrobial resistance as well as analysis of bacteria within the context of its environment. This symposium will explore these topics in detail as well as forecast future trends in mass spectrometry development that will provide more in-depth characterization of clinically-relevant microorganisms, their environmental milieu and their interaction with mammalian hosts.